Experimental validation confirmed that CD28 was significantly upregulated at both mRNA (<i>P</i> < 0.05) and protein levels (<i>P</i> < 0.001) in DSS-induced colitis mouse models.<h4>Conclusion</h4>Our findings suggest that HNF4A may be associated with T cell activation and potential regulation of CD28 in UC. Here, CD28 is linked to colitis.